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Volume 35, Issue 4
Displaying 1-16 of 16 articles from this issue
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Koiti TITANI1994 Volume 35 Issue 4 Pages 323-331
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSProteins are biopolymers which are directly involved in biological functions. Since their defects cause various diseases, proteins have been studied for a long time as the subjects of both basic and clinical medicine. Recent development of the genetic recombinant technique has made it possible to replace, add or delete any amino acid residue or any peptide portion in a protein. By utilizing this technique, we are now able to clarify more precisely than ever the structure and function relationship of a protein, and also to create various novel artificial proteins for the clinical use. In this article, I describe the proteins which are involved in blood coagulation and fibrinolysis and the regulation, and the current clinical application of the recombinant proteins. I also describe our new protein engineering technique for creation of artificial cell adhesive proteins by grafting the Arg-Gly-Asp Ser (RGDS) cell recognition signal, which was identified first in fibronectin and later in various plasma and extracellular matrix proteins. The physiological functions and possible clinical application of these artificial cell adhesive proteins thus created are also discussed.View full abstractDownload PDF (860K) -
[in Japanese]1994 Volume 35 Issue 4 Pages 332-335
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSDownload PDF (305K)
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Eiji KAJII, Toshinori OMI, Yasusada MIURA, Shigenori IKEMOTO1994 Volume 35 Issue 4 Pages 336-340
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSSixty four cases of autoimmune hemolytic anemia (AIHA) referred to our laboratory from 1985 to 1993 consisted of 51 warm type AIHA, 9 cold agglutinin disease (CAD), one paroxysmal cold hemoglobinuria, and 3 mixed type AIHA. There were 5 patients who had all clinical feautures of AIHA except for a positive direct-antiglobulin test (DAT). These patients were diagnosed as DAT-negative AIHA because of the elevation of red blood cell-associated IgG (RBC-IgG). The mean RBC-IgG of 100 healthy individuals was 33±13 (SD) molecules per one RBC. On the other hand, the RBC-IgG of patients with DAT-positive and with DAT-negative warm type AIHA were ranged from 257 to 12,421 and from 126 to 256 molecules per one RBC, respectively. One of 9 patients with CAD had a hemolytic anemia associated with only a cold agglutinin titer of 32 using saline-suspended RBCs, but a titer of 4,096 in the presence of bovine albumin. This case was diagnosed as low titer CAD. All of patients with DAT-negative AIHA or low titer CAD showed a good response to corticosteroid treatment.View full abstractDownload PDF (395K) -
Sumio MIYAZAKI1994 Volume 35 Issue 4 Pages 341-345
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSThe incidence of hemolytic uremic syndrome (HUS) has been increased for these several years. As the cause of HUS, verotoxin-producing E coli (VTEC) is very important. By our nationwide survey for five years from 1986 to 1990, 146 cases with HUS were compiled. Among 122 cases of HUS, 101 cases (82.8%) had good prognosis, 15 cases (12.3%) had renal or CNS residue. And death rate was 4.9% (6 cases). Clinical features were compared between the groups of good and poor prognosis. In the group of poor prognosis, impaired consciousness, convulsion and hypertension were significantly high. The data of biochemistry such as BUN, creatinine, GOT, GPT, C3, CH50 and CRP were significant between two groups. Demonstration of VTEC and positive serum antibody were seen in 60% among 35 cases. Dr Takeda of National Children's Hospital estimates that the incidence of hemolytic colitis is 1200 cases per year, and the occurrence of HUS is about 100 cases per year, among them 70% cases may be caused by VTEC.View full abstractDownload PDF (375K) -
Hideo WADA, Shigehisa TAMAKI, Shigeru SHIRAKAWA1994 Volume 35 Issue 4 Pages 346-351
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSWe examined various markers in 17 patients with thrombotic thrombocytopenic purpura (TTP), 13 with red cell fragmentation syndrome (RCFS) induced by mitomycin C, and 36 with RCFS caused by disseminated intravascular coagulation (DIC). A platelet activating facror and decrease of von Willebrand factor were frequently observed in patients with TTP, but were not in those with RCFS due to either mitomycin C or DIC. Since increased vascular endothelial cell markers and decreased MTT assay were observed in patients with TTP, it is considered that vascular endothelial cell injury is associated with patients with TTP. The increased plasma cytokines and the hypercoagulable and hypofibrinolytic state indicates that the vascular endothelial cell injury might be caused by microthrombus or activated immune system. Although patients with TTP were treated with plasma exchange, anti-platelet therapy, and high dose steroid therapy, the mortality was still high.View full abstractDownload PDF (426K) -
Haruhiko NINOMIYA1994 Volume 35 Issue 4 Pages 352-357
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSGlycosyl phosphatidylinositol (GPI)-anchored membrane proteins are deficient in the blood cells affected by paroxysmal nocturnal hemoglobinuria (PNH). The relation of the deficiencies of CD59 and CD14 with the clinical features of PNH are reported. CD59 binds to complement components C8 and C9 derived from human sera and inhibits the C5b-9-mediated hemolysis in a species-selective manner. The CD59-binding sites were revealed to be localized in the α subunit of C8 and in the “b” domain of C9 (thrombin fragment). The deficiency of CD59 in PNH is causatively related to the hemolytic features in PNH. A monocyte differentiation antigen, CD14, is deficient in the affected PNH monocytes. CD14 is reported to be one of the receptors to lipopolysaccharide (LPS). LPS-binding to the monocytes were revealed to be mediated through CD14 on monocytes. Enhancement of LPS-binding to monocytes by the presence of serum was not seen to PNH-affected monocytes. PNH-affected monocytes showed impaired TNF-α production in response to LPS. The deficiency of CD14 indicates the abnormality in PNH-affected monocytes, however, its significance in the clinical features of PNH is to be clarified.View full abstractDownload PDF (429K) -
Akihisa KANAMARU, Tomoko NISHIMURA1994 Volume 35 Issue 4 Pages 358-363
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSWe studied the expression of HRF20, one of the GPI-anchor proteins, on the hematopoietic progenitors and their progeny cells grown in cultures with bone marrow cells from patients with paroxysmal nocturnal hemoglobinuria (PNH). PNH bone marrow cells were sorted by fluorescence-activated cell sorter with anti-HRF20 monoclonal antibody and then cultured in methylcellulose. Every CFU-GM colonies and BFU-E bursts formed from the HRF20-negative fraction were HRF20-negative. On the other hand, there were HRF20-positive colonies and bursts as well as HRF20-negative ones in cultures with bone marrow cells from the HRF20-positive fraction. The results suggested that abnormal events can occur during the several steps of differentiation form PNH hematopoietic stem cells.View full abstractDownload PDF (379K)
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Yasuo TAKIMOTO, Akiro KIMURA1994 Volume 35 Issue 4 Pages 364-369
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSPDGF is a glycoprotein composed of A and B chains, and induced the expression not only in platelets but also in many types of cells. By stimulation inducing cell proliferation, transcription of the A chain is activated, resulting in an increase in mRNA. By stimulation inducing cell differentiation, the A chain is activated at the post-transcriptional level, and the B chain at the transcriptional level, resulting in an increase in both mRNA. The 5' region of the A chain shows a mosaic pattern of positive and negative regulatory elements, suggesting complicated regulation. Also the fragments of the first intron are bond by 110Kd and 90Kd nuclear proteins and regulate the A chain expression. Mechanisms of regulation of the A and B chain gene expression differ markedly. The role of PDGF was then investigated on the mechanism of myelofibrosis frequently observed in myeloproliferative disorders (MPD). In the chronic phase of MPD PDGF was suggested to be leaked or released from megakaryocytes. In the accelerated and blast phase of CML with fibrosis, PDGF-AB or PDGF-BB was found to be secreated from myeloid blasts. These results suggest the importance of PDGF in the pathogenesis of myelofibrosis associated with MPD.View full abstractDownload PDF (416K) -
Katsuhisa KOGAWA, Yoshihiro MOGI, Kazuhiro MORII, Rishuu TAKIMOTO, Yos ...1994 Volume 35 Issue 4 Pages 370-375
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSIn the present paper, we investigated the pathophysiological implication of TGF-β from megakaryocytes or megakaryoblasts in the development of myelofibrosis. In the bone marrow of myelofibrosis, proliferation of megakaryocytes is often noticed. We therefore investigated the TGF-β expression in the bone marrow megakaryocytes from 12 chronic myeloproliferative disorder patients with myelofibrosis by immunohistochemical analysis. About all the specimen showed strong positivity for TGF-β. In order to examine whether megakaryoblasts produce TGF-β, we then measured TGF-β activity in the conditioned medium (CM) of megakaryoblasts from a patient with acute megakaryoblastic leukemia who had profound myelofibrosis. The CM showed strong collagen synthesis stimulating activity which was nullified by addition of anti TGF-β antibody. Since TGF-β exists as latent form in platelets, TGF-β was considered to be altered from active to latent form during megakaryocytes differentiation. In this context, MEG-01, a megakaryoblastic cell line which produces active TGF-β was underwent differentiation to produce platelet-like bleb with TPA treatment. During the differentiation, MEG-01 showed the decrease of active TGF-β production and increase of latent TGF-β together with the production of LTBP. These results suggest that megakaryoblasts produce active TGF-β and may cause myelofibrosis, while more differentiated megakaryocytes produce latent TGF-β. Mechanism by which megakaryoblast escape from negative autocrine of active TGF-β was also investigated. MEG-01 was found to express mutated p53 which is considered to be responsible for impaired signal transduction of TGF-β.View full abstractDownload PDF (575K) -
Yasuhiro HOSODA, Yae KANAI1994 Volume 35 Issue 4 Pages 376-380
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSFrom 0.5 to 3 days after subcutaneous injection of monocrotaline (MCT) 60 mg/kg, prominent accumulation of platelets in the pulmonary capillaries accompanied with significant elevation of the plasma serotonin level was observed. To clarify the role of serotonin, the in vivo and in vitro effects of the selective 5-HT2 receptor antagonist, DV-7028, on MCT-induced pulmonary hypertension were studied. Oral administration of DV-7028 (10 mg/kg, twice daily) significantly suppressed the MCT-induced elevation of pulmonary arterial pressure, right ventricular hypertrophy and medial thickening of the muscular-type pulmonary arteries which occurred 23 days after MCT administration. The plasma level achieved by oral administration of 10 mg/kg DV-7028 was more than 10-7 M. The hyperreactivity to serotonin in isolated pulmonary artery segments from MCT-treated rats was significantly reduced by DV-7028 (10-7 M). The present study suggests that serotonin, released from platelets and accumulated in pulmonary capillaries, contributes to the initiation and/or progression of pulmonary hypertension in MCT-treated rats.View full abstractDownload PDF (399K) -
Masataka SASADA, Kousuke ASAGOE1994 Volume 35 Issue 4 Pages 381-385
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSInteractions between platelets and polymorphonuclear leukocytes (PMN) modulate their functions and play a role in the development of pathogenesis of some disease. Platelets secret various kinds of factors that affect PMN functions. They seemed to have important role in vivo, but little has been elucidated on exact mechanism of action and physiological meaning of each factor in relation to PMN functions. We studied the effects of platelets and released substances from activated platelets on the functions of PMN. Results were as follows. 1) Platelets enhanced bactericidal activities of PMN against E. coli. 2) Platelets had effects on the generation of superoxide anion (O2-) of PMN. Their effects were quite different according to the assay condition of PMN, that is, platelets inhibited O2- generation when PMN were at rest or stimulated slightly and they enhanced O2- generation of PMN that were stimulated with optimal condition. 3) Thrombin-activated platelets and their supernatant elicited a transient elevation of [Ca2+] of PMN. The activity of the supernatant decreased by treating with hexokinase that decomposed ATP. Further treatment with trypsin abolished its activity almost completely. Considering with our additional experiments, factors that induced [Ca2+] elevation of PMN were ATP, β-thromboglobulin and some trypsin-sensitive factor (s). 4) Supernatant of thrombin-activated platelts decreased random migration and chemokinesis of PMN.View full abstractDownload PDF (357K) -
—Molecular Cloning and Signal Transduction of PAF—Takashi IZUMI, Takao SHIMIZU1994 Volume 35 Issue 4 Pages 386-389
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSThe cDNA encoding the platelet-activating factor (PAF) receptor was cloned from a guinea pig lung cDNA library by using a Xenopus lavis oocyte expression system. In the CHO cells which expressed guinea-pig PAF receptor, PAF triggered production of inositol phosphates, the release of arachidonic acid, and inhibited cyclic AMP accumulation. PAF also activated mitogen-activated protein (MAP) kinase and MAP kinase kinase in the CHO cells. These effects were partially regulated by pertussis toxin-sensitive G proteins. The analysis of the human PAF receptor gene revealed that it contains no intron in its coding region, but introns are distributed in the 5'-untranslated region. Two 5'-noncoding exons were identified, which are alternatively spliced to a common splice acceptor site on the third exon to yield two different species of functional mRNA. Existence of distinct promoters may regulated the PAF receptor gene expression in different tissues and cells.View full abstractDownload PDF (309K)
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Tatsuharu OHNO, Yoichi SAKA, Juu HORII, Tateo SUGIYAMA, Fumihiko INOUE ...1994 Volume 35 Issue 4 Pages 390-396
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESS62-year-old female, who had been under observation for an indolent myeloma for six years without therapy, was admitted because of left flank pain. Various imaging modalities disclosed left pleural effusion, and a huge abdominal tumor involving the left crus of the diaphragm, spleen, stomach, pancreatic tail, left adrenal gland, left kidney and left posterior abdominal wall. Morphological and immunological examinations revealed extensive proliferation of more anaplastic myeloma cells within the tumor and in the pleural effusion than those in bone marrow on admission or at the beginning of the period of observation. Chemotherapy reduced serum M-protein, but LDH, the volume of the pleural effusion, and the size of the tumor increased. She died of pancreatitis associated with massive bleeding from the gastric tumor. Renal function was well preserved until her terminal phase. The clinical course showed the progression of indolent myeloma into an aggressive one without chemotherapeutic intervention, implying a rare subtype in terms of the natural history of multiple myeloma.View full abstractDownload PDF (698K) -
Hiraku MORI, Naoki TAKAHASHI, Junichi TADA, Takakazu HIGUCHI, Tohru SH ...1994 Volume 35 Issue 4 Pages 397-402
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSA 19 years old male admitted to our hospital with fever, abdominal pain in May 1991. Physical examination revealed anemia, jaundice and marked splenomegaly. Severe pancytopenia with macrocytic hyperchronic anemia was noted along with elevated LDH and reduced serum folate. Blood smear showed nucleated RBCs, but only few microspherocytes. Bone marrow showed erythroid hyperplasia with remarkable megaloblastic changes. Megaloblasts were negative for PAS stain. Chromosome analysis revealed normal karyotype. Erythroleukemia was suspected initially, but his general condition as well as hematological data improved following 10 units of RBC transfusion. Following brief folic acid supplements, numerous microspherocytes became evident, typical osmotic fragility test revealed a pattern for hereditary spherocytosis. These observations led us to the diagnosis of hereditary spherocytosis complicated by megaloblastic anemia due to folate deficiency. As he developed folate deficiency again 10 months later, splenectomy were performed. The anemia improved after splenectomy.View full abstractDownload PDF (479K) -
Kazuki KOIZUMI, Sigeki HIRAYAMA, Hina TAKANO, Norihiro SATO, Atsushi N ...1994 Volume 35 Issue 4 Pages 403-408
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSA 30-year-old female was admitted to our hospital complaining of high fever and fatigue. Laboratory findings showed as follows; WBC 41,500/μl (40% of blasts), Hb 8.5g/dl, platelets 4.4×104/μl. Cytochemical staining of blasts was positive for peroxidase and non-specific esterase with NaF inhibition. Chromosome analysis showed 46, XX, inv (16p+, q-). AML with eosinophilia was diagnosed. During myelosuppression after remission induction therapy, she developed high fever, and did not respond to transfusions. Marrow smears showed the presence of phagocytic histiocytes consisting of 18% total nuclear cells. A diagnosis of reactive histiocytosis (RH) was made. She recovered spontaneously, but suffered two episode of recurrence during subsequent chemotherapy. Reactive histiocytosis is characterized by proliferation of histiocytes which phagocyte blood cells in immunodeficient cases, e.g. a myelosuppressive state after chemotherapy. RH causes high fever and prolonged myelosuppression. It is considered to be one of the poor prognostic factors in AML during chemotherapy, and spontaneous recovery is rare. In this report, the effect of hydrocortisone on histiocytes derived from patient marrow was also investigated in vitro.View full abstractDownload PDF (502K)
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1994 Volume 35 Issue 4 Pages 409-413
Published: 1994
Released on J-STAGE: April 25, 2009
JOURNAL RESTRICTED ACCESSDownload PDF (428K)
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